The invention disclosed herein is generally related to methods for producing radioisotopes for use in diagnostic and experimental medical applications. More particularly, the present invention is related to methods for producing and isolating the short-lived radioactive isotope .sup.67 Cu.
Copper is a biologically important element which is present in low concentrations in virtually all biological systems. Radioactive isotopes of copper are useful for studying the metabolism of copper in such systems. One such isotope is .sup.67 Cu, which is particularly useful because it is easily detected at low concentrations by gamma ray spectroscopy, and also because it has a decay rate which is particularly convenient for use in radiochemical applications. In this regard, the half-life of .sup.67 Cu is 61.9 hours, which is sufficiently long to permit the isotope to be produced, shipped to an end user, and used for its intended purpose before it decays. At the same time, such a half life is sufficiently short that the isotope decays substantially completely over a period of a few weeks, thus avoiding the difficulties ordinarily associated with the disposal of radioactive waste.
Other short-lived radioactive isotopes of copper include .sup.64 Cu, with a half-life of 13 hours, and .sup.61 Cu, with a half-life of 3.3 hours. Each of these isotopes is too short-lived to permit it to be produced and shipped to a distant user.
In medical tracing applications, it is often desirable to use as small an amount of radioactive tracer as possible. This is because it is desirable not to disturb the natural chemical equilibrium of a living biological system, such as would result from injecting a large amount of a chemical element. When the normal equilibrium of a living system is overwhelmed with a large quantity of an element, the natural biological elimination mechanisms operate to collect and excrete the element, such that it cannot be traced in the course of its ordinary metabolism. Consequently, it is desirable to use a radioactive tracer which has a sufficiently high activity to permit the detection and location of very small amounts of the tracer within a biological system. When such a radioactive nuclide is substantially free of stable isotopes of the same element, it is referred to as being carrier-free.
One well known method of producing artificial nuclides utilizes low energy charged particle accelerators. Such accelerators can be used to synthesize various nuclides by inducing the capture of accelerated particles by target nuclides. By such a method, the isotope .sup.67 Cu could conceivably be produced through a (p, 2p) reaction by bombarding .sup.68 Zn with protons; or through a (d, 2p) reaction by bombarding .sup.67 Zn with deuterons; or through a (.alpha., 2p) reaction by bombarding .sup.65 Cu with alpha particles. However, none of these reactions is of practical interest, either because of the high cost of the enriched isotope species or a low reaction cross section, or both, and to date there has been no practical method of producing significant amounts of .sup.67 Cu with a low energy charged particle accelerator.
Another technique that has been previously used to produce synthetic nuclides is the double neutron capture method. This method is conducted in the high neutron flux of a nuclear reactor, and uses two successive (n,.gamma.) reactions. Stable .sup.65 Cu would be used to produce .sup.67 Cu by this method. Such a method is not feasible, however, because the intermediate nuclide, .sup.66 Cu, is unstable, with a 9 minute half-life. Also, this technique would only produce .sup.67 Cu mixed with large amounts of stable copper, thus diminishing its value for medical tracing applications.
.sup.67 Cu has previously been produced by neutron bombardment of .sup.67 Zn in a nuclear reactor. The .sup.67 Zn undergoes a (n,p) reaction to produce .sup.67 Cu directly. More specifically, the .sup.67 Zn captures a neutron to form .sup.68 Zn, which then decays by emission of a proton to give .sup.67 Cu. This method requires the use of isotopically enriched .sup.67 Zn as the starting material, which is very expensive and available only in small quantities. In such a reaction, 100 mg of 97% enriched .sup.67 Zn (purchased at a typical price of approximately $1,000 per gram) is irradiated for approximately 72 hours in a fast neutron flux of 10.sup.15 neutrons/cm.sup.2 -sec. However, the reaction has a cross-section of approximately 0.82 millibarns, which represents a relatively low reaction probability. Also, the probability of an (n,.gamma.) reaction in the target .sup.67 Zn, which produces .sup.68 Zn, is much higher than the probability of the (n,p) reaction, with the result that much more .sup.68 Zn than .sup.67 Cu is formed. Thus, the (n,p) reaction has a very low yield, but has nevertheless been the only method previously available for making .sup.67 Cu. The expensive .sup.67 Zn target was essentially consumed in each reaction run, forming unwanted .sup.68 Zn and only small amounts of .sup.67 Cu. In a typical run 12 millicuries of .sup.67 Cu were formed, as opposed to yields on the order of a curie with the method of the present invention described below.
It will be further recognized that the relatively short half-life of .sup.67 Cu, less than three days, requires that any process of producing .sup.67 Cu by a nuclear reaction must be combined with a process of chemical separation and purification that is sufficiently rapid to permit prompt preparation of the .sup.67 Cu in a form suitable for medical use and shipping of the isotope to distant medical facilities.
It has been known for some time that high energy charged particle accelerators are capable of producing various nuclides by spallation reactions. In such a reaction a target nuclide is impacted with high energy particles, which do not combine with the target nuclide as in the case of the low energy particle accelerators mentioned above, but rather decompose the target nuclide by spallation to produce a variety of nuclides which are generally of both lower atomic weight and lower atomic number than that of the target nuclide. However, until recently there have not been available high energy accelerators with sufficient beam current capacity to produce significant quantities of nuclides by spallation reactions. The advent of high current proton accelerators, such as the Meson Physics Facility as the Los Alamos National Laboratory, made it feasible to pursue the production of nuclides such as .sup.67 Cu in significant quantities by proton spallation. At the same time, however, the selection of suitable target materials for this purpose was complicated by certain problems associated with the high current accelerators, particularly the high temperatures generated in the target and the production of significant amounts of radioactive byproducts. Such byproducts hinder the rapid chemical separation of short-lived nuclides after the target is removed from the accelerator.
For example, arsenic and selenium were thought to be feasible target materials for producing .sup.67 Cu, on the basis of their atomic numbers and weights. However, heat calculations and irradiation experience indicated that these elements would be likely to vaporize from any target compound in which they might be incorporated, possibly causing the irradiation container to burst under the high temperature conditions of the target. In this regard, it is noted that the Los Alamos Meson Physics Facility presently produces a beam of protons having an energy of 800 MeV at a current of 700 microamps, which represents a power input into a single target of approximately 10 to 15 kilowatts.
Gallium would also be a feasible target material in view of its atomic number and weight, but it is particularly difficult to separate chemically from the resulting .sup.67 Cu.
Another material which was considered for use as a target in producing .sup.67 Cu was rubidium bromide. RbBr was considered particularly suitable because both Rb and Br will produce .sup.67 Cu by proton spallation reactions. However, upon testing RbBr as a target it was found that radioactive gaseous krypton is a significant fragmentation product of the spallation reaction. The production of radio-krypton requires a period of decay prior to target dissolution, with accompanying unacceptable delays in the chemical separation of the short-lived .sup.67 Cu.